Viral and bacterial infections are frequently highly contagious, especially when spread by respiration. The recent reports regarding Severe Acute Respiratory Syndrome (“SARS”), now known to be caused by a corona virus, are proof of how rapidly an infection can spread when it is transmitted through air contact. Other diseases such as influenza spread by air contact, and rapidly reach epidemic proportions, with high numbers of fatalities in elderly and immunocompromised populations.
SARS is a respiratory illness that has recently been reported in Asia, North America, and Europe. As of Apr. 20, 2003, about 198 suspect cases of SARS and 38 probable cases of SARS had been reported in the United States. In general, SARS begins with a fever greater than 100.4° F. [>38.0° C.]. Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some people also experience mild respiratory symptoms. After 2 to 7 days, SARS patients may develop a dry cough and have trouble breathing.
SARS appears to spread primarily by close person-to-person contact. Most SARS cases have involved people who cared for or lived with someone with SARS, or had direct contact with infectious material (for example, respiratory secretions) from a person who has SARS. Potential ways in which SARS can be spread include touching the skin of other people or objects that are contaminated with infectious droplets and then touching your eye(s), nose, or mouth. This can happen when someone who is sick with SARS coughs or sneezes droplets onto themselves, other people, or nearby surfaces. It is also possible that SARS can be spread more broadly through the air or by other ways that are currently not known. At present there is no treatment or means of prevention for SARS, other than supportive care.
TB, or tuberculosis, is a disease caused by the bacteria Mycobacterium tuberculosis. The bacteria can attack any part of the body, but usually attacks the lungs. TB was once the leading cause of death in the United States. In the 1940s, scientists discovered the first of several drugs now used to treat TB. As a result, TB slowly began to disappear in the United States. Recently, TB has made a resurgence. Between 1985 and 1992, the number of TB cases increased, with more than 16,000 cases reported in the United States in 2000 alone.
TB is spread through the air from one person to another. The bacteria are dispersed into the air when a person with TB of the lungs or throat coughs or sneezes. People nearby may breathe in these bacteria and become infected. When a person breathes in Mycobacterium tuberculosis, the bacteria can settle in the lungs and begin to grow. From there, it can spread through the blood to other parts of the body, such as the kidney, spine, and brain. People with TB are most likely to spread it to people they come in contact with on a daily basis. People who are infected with latent TB do not feel sick, are asymptomatic, and cannot spread TB, but they may develop TB at some time in the future.
Bacteria are not the only sources of infectious diseases. Viruses are also highly contagious and have no effective treatments other than containment. For example, Respiratory syncytial virus (RSV) is a very common virus that causes mild cold-like symptoms in adults and older healthy children. By age two, nearly all infants have been infected by RSV. RSV can cause severe respiratory infections in infants, particularly those born prematurely, with heart or lung disease, or immunocompromised. Seasonal outbreaks of acute respiratory illness typically occur in the fall and last into the spring. RSV is spread easily by physical contact. Transmission is usually by contact with contaminated secretions, called foamites, which may involve tiny droplets or objects that droplets have touched. RSV can live for half an hour or more on human hands. The virus can also live up to five hours on countertops and for several hours on used tissues. RSV often spreads very rapidly in crowded households and day care centers. Each year up to 125,000 infants are hospitalized due to severe RSV disease, and about 1-2% of these infants die. It has been reported that exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis was beneficial (Tibby, et al. Am J Respir Crit Care Med October 2000; 162(4 Pt 1):1251). The principle means of treatment remains supportive however, and there is no means of limiting spread other than isolation.
Influenza is another common viral infection for which there is no effective treatment, and containment is the only option to limit spread of disease. Influenza is caused by three viruses—Influenza A, B and C. Type A is usually responsible for large outbreaks and is most adept at mutating. New strains of Type A virus develop regularly and cause new epidemics every few years. Type B causes smaller outbreaks, and Type C usually causes mild illness. In the United States, infection with influenza A and B leads to 20,000 deaths and over 100,000 hospitalizations each year. Influenza is transmitted person to person via contagious droplets that are formed when someone sneezes or coughs.
Approximately 8 million children and adolescents between 6 months and 17 years of age have one or more medical conditions that put them at increased risk of influenza-related complications. Such children include those with chronic disorders of the heart or lungs (such as asthma and cystic fibrosis), children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), kidney dysfunction, sickle cell anemia, or immunosuppression.
For unvaccinated individuals who have been exposed to people with known influenza, especially if the exposed individual has risk factors, potential use of antiviral medication for more than 2 weeks and vaccination may help prevent illness. For mild illness in people who are not at high-risk, the treatment of influenza is frequently just supportive and includes bed rest, analgesics for muscle aches and pains, and increased intake of fluids. Treatment is usually not necessary for children, but may be prescribed if the illness is diagnosed early and the patient is at risk of progression to more severe infection. Among individuals in high-risk groups (elderly, immunosuppressed, chronic heart, lung or kidney conditions) influenza may be quite severe and can lead to complications or death.
Epidemics of respiratory infections are not limited to humans. Foot-and-mouth disease virus (FMDV) is the etiologic agent of foot-and-mouth disease (FMD), which is a disease of cattle, swine, and other cloven-footed animals. FMD is characterized by the formation of vesicles on the tongue, nose, muzzle, and coronary bands of infected animals. Several unique characteristics make the virus one of the most economically devastating diseases in the world today. The ease with which it may be transmitted by contact and aerosol, combined with its enhanced ability to initiate infections, virtually ensures that most, if not all, animals in a herd will contract FMD. The long-term survival of FMDV in infected animals' tissues and organs, especially when refrigerated, offers an opportunity for its national and international transmission through the food chain. Multiple serotypes and numerous subtypes reduce the effectiveness and reliability of vaccines. The possible development of carriers in vaccinated animals and those that have recovered from FMD provides additional potential sources of new outbreaks. These features create a disease that can have a major economic impact on live stock operations around the world. The foot and mouth disease (FMD) epidemic in British livestock remains an ongoing cause for concern, with new cases still arising in previously unaffected areas (Ferguson, et al., Nature 2001 414(6861):329). The parameter estimates obtained in a dynamic model of disease spreading show that extended culling programs were essential for controlling the epidemic to the extent achieved, but demonstrate that the epidemic could have been substantially reduced in scale had the most efficient methods been used earlier in the outbreak.
Viral shedding through bioaerosol exhalation is one mechanism, for infection transmission from a host leading to inhalation by another animal or human. The devastating consequences that uncontrolled viral shedding can have on livestock were seen in the hoof and mouth disease outbreak in the U.K., where 2030 confirmed cases resulted in the mandatory slaughter of 4 million animals. Recently, more attention is being given to the threat of bioterrorism and the similar risk that a sudden outbreak of disease poses to livestock in the U.S.
Airborne infection is one of the main routes of pathogen transmission. Aerosols composed of mucus droplets originating in the lungs and nasal cavities are produced when a human or animal coughs or simply breathes. These bioaerosols can contain pathogens that transmit the disease upon inhalation by exposed humans or animals. In addition, respirable pathogenic bioaerosols produced in the upper airways can be re-breathed by the host leading to parenchymal infection with exacerbated disease outcomes.
WO03/092654 to David Edwards et al. describes a method for diminishing the spread of inhaled infections by delivering materials such as surfactants that suppress bioaerosol expiration. This technique works on the basis of altering the surface or other physical properties of the endogenous surfactant fluid in the lungs, and thereby favoring fewer exhaled bioaerosol particles. It would be desirable to have other means of limiting bioaerosol formation and/or spread.
It is therefore an object of the present invention to provide formulations for use in decreasing or limiting spread of pulmonary infections, especially viral or bacterial infections, without delivery of surfactant material to the lungs.
It is further an object of the present invention to provide a method of treatment to decrease or limit the spread of pulmonary infections to other animals or humans, especially viral or bacterial infections.
It is further an object of the present invention to provide a method of treatment to decrease or limit the spread of pulmonary infections, especially viral or bacterial infections, within a patient.
It is further an object of the present invention to provide formulations for treatment of humans or animals to limit infectivity.
It is yet a further object of this invention to manufacture a device for the measurement of exhaled particle number and particle size to diagnose those animals or humans, with an enhanced propensity to exhale aerosols.